An association between RA and alleles of the HLA-DRB1 locus has long been established84. Despite extensive linkage85-87 and association studies, only one other RA susceptibility locus has been convincingly identified in Caucasians. In common with several autoimmune diseases including T1D, carriage of the T allele of the rs2476601 SNP in the PTPN22 (protein tyrosine phosphatase, non-receptor type 22) gene has been reproducibly associated with RA, conferring a genetic relative risk of approximately 1.8 (refs 88, 89). These known associations with HLA-DRB1 and PTPN22 explain around 50% of the familial aggregation of RA.
